The development of strategies for specifically enhancing the radio- sensitivity of tumor cells would be expected to significantly impact on the success of cancer treatment. Over the last 10 years considerable evidence has accumulated establishing a role for ras mutation and/or over-expression in protecting cells against radiation-induced death. As a novel approach to radiosensitization, we are proposing to investigate the use of an adenovirus expressing a single chain antibody fragment (scFv) directed against Ras proteins, referred to as AD1Y28. Our preliminary results indicate that exposure to AD1Y28 increases tumor cell radiosensitivity, yet has no effect on the radioresponse of normal cells in vitro. Furthermore, this radio- sensitization appears to be the result of an enhanced susceptibility of tumor cells to radiation-induced apoptosis. The proposed experiments will expand these initial observations to additional human tumor cell lines to further evaluate the influence of ras mutational status and the role of apoptosis in AD1Y28-mediated radiosensitization. Studies will then be extended to the in vivo situation combining AD1Y28 with single and fractionated doses of radiation against using human tumor cell xenografts grown in nude mice. The overall goal of these investigations is to generate specific information regarding the therapeutic potential of the AD1Y28/radiation combination. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE